Epidermal Growth Factor (EGF) is a widely distributed endogenous polypeptide (King). It is a powerful mitogen with high affinity receptors in both fibroblasts and epidermal keratinocytes, and has been shown to accelerate wound healing in vivo (O'Keef; Knauer). The first 5-10 days after injury are the most critical period during which maximal differences are seen between EGF treated and untreated wounds. EGF application after this period produces no significant improvement over controls, since by this time reepithelialization has already occurred in both groups. Due to its relatively short half life of about one hour, (Buckley, 1987), loss of occupied receptors through turnover and a lag time of 8-12 hours to commit cells to DNA synthesis (Knauer), it is necessary to apply EGF frequently to a wound to maintain effective local concentration during the critical period of initial wound healing (Buckley, 1987; Buckley, 1985; and Franklin, 1986). Thus, effective EGF therapy depends on frequent or sustained application of the drug during the first several days of wound healing.
For superficial wounds, local concentration of EGF can easily be maintained by frequent applications. For surgical incisions and full thickness skin wounds requiring suture repair, frequent application is not possible and a sustained-release formulation of EGF must be used for these uses. Implanted sponges have demonstrated the advantages of sustained EGF release in an animal wound model (Buckley, 1985) but would not be suitable as a dosage form.